The aim of the program is to identify control mechanisms underlying normal and defective mammalian development, especially with respect to abnormalities or diseases due to mutant genes. These problems are being investigated in the following experimental systems: (1) Allophenic mice, in which cells of different genotypes (e.g., normal and defective) coexist from early embryonic life onward, are being used to probe the developmental basis for genetically caused anemias, for hereditary autoimmune disease, for genetic susceptibility to tumorigenesis, for aging, and for cell lineages in relation to brain organization and neurological defects. (2) Transplantable testicular and ovarian teratomas, containing multipotential stem cells, are serving as material for in vitro testing of environmental (e.g., substratum) effects on cell diversification, and for identification of early embryo antigens. (3) Control of embryo implantation is being studied with respect to a uterine proteinase product which appears to initiate embryo attachment to the uterine wall. (4) Transmission and expression of oncogenic viral nucleic acids is being explored by means of microinjection of purified DNA into early mouse embryos which are allowed to develop to adult life.